Dr. Zavala has previously demonstrated that it is difficult to generate antigen- specific secondary CD8 and CD4 T cell responses in mice that have undergone a single round of immunization with irradiated malaria sporozoites. The induction of strong memory responses to malaria antigens is considered an important goal to be achieved by immunization with subunit or live-vectored candidate malaria vaccines. He proposes to identify parameters which reflect protective antiparasite activity of CD8 T cells; to characterize optimal conditions to establish efficient effector and memory CD8 responses; identify mechanisms that regulate in vivo expansion of memory CD8 T cells; to determine the role of antigen persistence in memory induction; to use recombinant vaccinia vectors expressing cytokines and malaria antigens to define optimal conditions to enhance duration of malaria protection.